Hyperopic reserve as a predictor of myopia progression: LAMP2 study

Paper title: Hyperopic Reserve as an Indicator of Myopia Prevention by Atropine (Low-concentration Atropine for Myopia Prevention Study)

Authors: Zhang XJ (1,7), Zhang Y (1), Yip BHK (6), Kam KW (1,3), Ng MPH (1), Wong ICK (8), Ip P (9), Young AL (1,3), Tham CC (1,2,3,4,5,7), Chen LJ (1,3,4), Pang CP (1,4,7), Yam JC (1,2,3,4,5,7)

1. Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
2. Hong Kong Eye Hospital, Hong Kong SAR, China
3. Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China
4. Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China
5. Department of Ophthalmology, Hong Kong Children’s Hospital, Hong Kong SAR, China
6. Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
7. Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China
8. Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong SAR, China
9. Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR, China

Date: Published online June 12, 2024

Reference: Zhang XJ, Zhang Y, Yip BHK, Kam KW, Ng MPH, Wong ICK, Ip P, Young AL, Tham CC, Chen LJ, Pang CP, Yam JC. Hyperopic reserve as an indicator of myopia prevention by atropine (Low-concentration Atropine for Myopia Prevention Study). Ophthalmology. 2024 Nov;131(11):1347-1349.

[Link to article]

The LAMP2 study demonstrated that 0.05% atropine can delay myopia onset by 47% over two years, but not all children are at equal risk of developing myopia.

This secondary analysis aimed to identify factors influencing treatment efficacy, including age, baseline hyperopic reserve, and family history, to determine which children would benefit most from prophylactic atropine treatment, minimising unnecessary intervention. 

The LAMP2 study was a randomized, placebo-controlled, double-masked trial including non-myopic children aged 4 to 9 years with baseline spherical equivalent refraction (SE) between +1.00 D and 0.00 D. Participants received 0.05% atropine, 0.01% atropine, or placebo once nightly for two years, with cycloplegic refraction and axial length (AL) measurements taken at follow-up visits.

Key findings:

• Younger children showed greater axial length growth, though this was not linked to spherical equivalent progression or myopia onset.
• Children with lower baseline hyperopic reserve were at higher risk of developing myopia and showed greater treatment benefits.
• 0.05% atropine was more effective in delaying myopia onset than 0.01% or placebo, particularly in children with less hyperopic reserve.

These results suggest that targeting children with low hyperopic reserve and a family history of myopia for early atropine intervention may optimize treatment outcomes.

1. This study reinforces that not all children require preventive atropine treatment and that identifying high-risk individuals can improve treatment efficiency. Children with lower hyperopic reserve and a strong family history of myopia should be prioritized, as they face a higher risk of progression.
2. Younger children showed greater axial elongation in the study, but the association with myopia onset remains unclear. Identifying axial length and refraction changes in younger children will be critical in refining early intervention strategies for myopia prevention, even if their spherical equivalent appears stable.
3. Although 0.05% atropine showed greater efficacy over 0.01% concentration and the placebo drop, particularly in children with minimal hyperopic reserve, prescribing atropine to children with significant hyperopic reserve may not be necessary. Eye care practitioners should consider hyperopic reserve and parental myopia and incorporate them into myopia risk assessments to ensure targeted treatment.

This study focused on children with hyperopic reserves between 0 D and +1.0D, meaning the effectiveness of 0.05% atropine in children with higher levels of hyperopia is still unknown. Future research could establish if there is an optimal hyperopic reserve threshold which aids patient selection, maximises benefit and minimises unnecessary treatment.

The participant dropout rate was higher than expected, partly due to external factors such as the COVID-19 pandemic. While sensitivity analyses suggest this did not affect results, long-term studies with a larger cohort are needed to confirm the results in a wider population.

Younger age was associated with faster axial elongation but not myopia onset or SE progression. Further investigation is required to determine whether early intervention should be adjusted based on age-related differences in treatment response, if the same efficacy is achievable for age-matched children of different ethnicities who have different progression rates and how faster progression rates in younger children might impact the treatment response. 

Title: Hyperopic Reserve as an Indicator of Myopia Prevention by Atropine (Low-concentration Atropine for Myopia Prevention Study)

Authors: Xiu Juan Zhang, Yuzhou Zhang, Benjamin H.K. Yip, Ka Wai Kam, Mandy P.H. Ng, Ian C.K. Wong, Patrick Ip, Alvin L. Young, Clement C. Tham, Li Jia Chen, Chi Pui Pang, Jason C. Yam

Purpose: The Low-concentration Atropine for Myopia Prevention (LAMP2) study has shown that 0.05% atropine eye drops can delay the onset of myopia by 47% over 2 years. However, not all children are at equal risk of developing myopia, and therefore a targeted approach to minimize unnecessary treatment for those who will not develop myopia is needed. To address this research gap, we evaluate factors associated with the efficacy of low-concentration atropine in delaying myopia onset to identify who will benefit from this prophylactic intervention.

Main Outcomes and Measures: The outcome measures included (1) factors associated with myopia onset, SE progression, and AL elongation over 2 years; and (2) the SE progression and AL elongation over 2 years in various baseline hyperopic reserve.

Methods: The participants who completed a 2-year follow-up in the LAMP2 study were included. In the original LAMP2 study, participants were nonmyopic children aged 4 to 9 years with a cycloplegic spherical equivalent (SE) between +1.00 and 0.00 diopters (D) who were randomized into groups that received 0.05% or 0.01% atropine or placebo eye drops once nightly in both eyes.

Results:  Over 2 years, low baseline hyperopic reserve and high level of parental myopia increased the risk of myopia onset (odds ratio, 0.02, P < 0.001 and odds ratio, 2.29, P = 0.003, respectively), SE progression (β = 0.45, P < 0.001 and β = –0.22, P = 0.003, respectively) and AL elongation (β = –0.22, P < 0.001 and β = 0.08, P = 0.01, respectively). Younger age was associated with AL elongation (β = –0.08, P < 0.001), but not SE progression or myopia onset. Subgroup analysis found that in the 0.05% atropine group, the SE progression over 2 years was similar across groups with various baseline hyperopic reserve. However, in the 0.01% atropine and placebo groups, the SE progression was affected by the baseline hyperopic reserve, with the lower baseline hyperopic reserve the faster the progression (P trend < 0.001 in both groups). Similar trends were observed for AL elongation. This indicates that 0.05% atropine is more effective than 0.01% or placebo for eyes with less hyperopic reserve. Among participants with the baseline hyperopic reserve of less than +0.75 D, the SE progression over 2 years was less with 0.05% atropine than with placebo (adjusted differences from 0.55 D to 0.92 D, P values < 0.001) and with 0.01% atropine (adjusted differences from 0.45 D to 0.69 D, P values < 0.01). Among participants with a baseline hyperopic reserve of +1.0 D to +0.75 D, the SE progression had no significant difference in all treatment groups. Similar relationships were observed in AL elongation over 2 years

Conclusions:. Consistent with previous studies, children with less hyperopic reserve and high level of parental myopia were at a higher risk to develop myopia. Preventive treatment with low-concentration atropine should be targeted to them. Although starting low-concentration atropine in eyes with preserved hyperopic reserve likely would result in a lower likelihood of progressing to myopia, 0.05% atropine is more effective than 0.01% or placebo for eyes with less hyperopic reserve.

[Link to article]